ao9b03917_si_001.pdf (2 MB)
Supercritical CO2 Processing Generates Aqueous Cisplatin Solutions with Enhanced Cancer Specificity
journal contribution
posted on 2020-02-24, 18:07 authored by Sudhir
Kumar Sharma, Sumaya Al Hosani, Mona Kalmouni, Anjana Ramdas Nair, Loganathan Palanikumar, Renu Pasricha, Kirsten C. Sadler, Mazin Magzoub, Ramesh JagannathanCisplatin is a highly
toxic material used clinically as a potent
chemotherapeutic. While effective against some cancers, toxicity limits
widespread use and low solubility confounds delivery. To formulate
a better tolerated and more water-soluble form of cisplatin, we designed
a rapid expansion of supercritical solutions (RESS) technique with
supercritical carbon dioxide (sc-CO2) to collect nanoclusters
of cisplatin embedded in dry ice, in a dual-stage collection vessel
cooled to liquid nitrogen temperature. These nanoclusters were solubilized
in deionized water and further concentrated (up to 51.3 mM) by a Rotovap
process, yielding stable cisplatin solutions with solubility up to
15 × (w/w) greater than that of normal cisplatin. Extensive material
characterizations of the solutions were carried out to determine any
chemical and/or structural changes of the RESS-processed cisplatin.
In vitro cytotoxicity studies of these aqueous solutions showed increased
cell viability and early apoptosis compared to equivalent concentrations
of standard cisplatin solutions. In vivo studies using zebrafish embryos
revealed that standard cisplatin solutions were acutely toxic and
caused death of rapidly proliferating cells compared to RESS-processed
cisplatin, which were better tolerated with reduced general cell death.
Increased water solubility and matched chemical identity of RESS-processed
aqueous cisplatin solutions indicate the potential to open up novel
drug-delivery routes, which is beneficial for new pharmaceutical design
and development.